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BACKGROUND: Current treatment for chronic kidney disease (CKD) focuses on improving manifestations and delaying progression. Nutritional approaches play a crucial role in CKD management, and various supplements have become available. Ketoanalogues of amino acids (KAs), calcium citrate, and inulin have been proposed as suitable supplements, yet their widespread use has been limited due to insufficient evidence. This study aimed to generate general guidance statements on the appropriateness of these supplements through a RAND/UCLA consensus process. METHODS: A RAND/UCLA consensus panel was convened to evaluate the appropriateness of these supplements in different clinical scenarios. In this study, we present a subgroup analysis focusing on a panel of eleven clinical nephrologists from among the experts. RESULTS: Supplementation of low-protein diets (LPDs) and very low-protein diets (VLPDs) with KA was considered appropriate to reduce manifestations and delay CKD outcomes, supplementation with calcium citrate is considered appropriate to reduce CKD manifestations, and supplementation with inulin is considered appropriate to delay CKD outcomes and manage comorbidities. CONCLUSIONS: Based on a combination of clinical experience and scientific evidence, the panel reached a consensus that KA supplementation of LPD and VLPD, calcium citrate, and inulin are appropriate in patients with CKD across various scenarios.

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INTRODUCTION: Heart exploration is an essential clinical competence that requires continuous training and exposure. Low availability and accessibility to patients with heart disease constitutes a barrier to acquiring this competence. Inadequate cardiac auscultation skills in medical students, residents, and graduate physicians have been documented. OBJECTIVE: To develop and validate a low-cost, high-fidelity simulator for heart exploration. METHODS: A low-cost, high-fidelity heart examination simulator capable of reproducing normal cardiac sounds was designed and developed. Subsequently, the simulator was validated by a group of experts who gave their opinion according to a Likert scale. RESULTS: Ninety-four percent agreed that the simulator motivates the learning of heart exploration, and 92 % considered it to be a realistic model; 91 % considered that the simulator is an attractive tool to reinforce learning and 98 % recommended its further use. CONCLUSIONS: The use of the simulator facilitates the acquisition of skills and stimulates learning in the student, which can be attributed to repeated practice, longer exposure time and cognitive interaction.

INTRODUCCIÓN: La exploración cardiaca es una competencia clínica fundamental que requiere exposición o entrenamiento continuo. La baja disponibilidad y accesibilidad de pacientes con patología cardiaca constituye una barrera para adquirir esta competencia. Se han documentado inadecuadas habilidades de auscultación cardiaca en estudiantes de medicina, residentes y médicos graduados. OBJETIVO: Elaborar y validar un simulador de alta fidelidad y bajo costo para exploración cardiaca. MÉTODOS: Se diseñó y elaboró un simulador para exploración cardiaca, realista y de bajo costo capaz de reproducir ruidos cardiacos normales. Posteriormente se realizó la validación del simulador por un grupo de expertos que emitieron su opinión de acuerdo con una escala tipo Likert. RESULTADOS: El 94 % afirmó que el simulador motiva el aprendizaje de la exploración cardiaca y 92 % lo consideró un modelo realista; 91 % consideró que el simulador es una herramienta atractiva para fortalecer el aprendizaje y 98 % recomendó seguir utilizándolo. CONCLUSIONES: El uso del simulador facilita la adquisición de competencias y estimula el aprendizaje en el estudiante, lo cual puede ser atribuido a la práctica deliberada, a un mayor tiempo de exposición y a la interacción cognitiva.

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Resumen Introducción: La exploración cardiaca es una competencia clínica fundamental que requiere exposición o entrenamiento continuo. La baja disponibilidad y accesibilidad de pacientes con patología cardiaca constituye una barrera para adquirir esta competencia. Se han documentado inadecuadas habilidades de auscultación cardiaca en estudiantes de medicina, residentes y médicos graduados. Objetivo: Elaborar y validar un simulador de alta fidelidad y bajo costo para exploración cardiaca. Métodos: Se diseñó y elaboró un simulador para exploración cardiaca, realista y de bajo costo capaz de reproducir ruidos cardiacos normales. Posteriormente se realizó la validación del simulador por un grupo de expertos que emitieron su opinión de acuerdo con una escala tipo Likert. Resultados: El 94 % afirmó que el simulador motiva el aprendizaje de la exploración cardiaca y 92 % lo consideró un modelo realista; 91 % consideró que el simulador es una herramienta atractiva para fortalecer el aprendizaje y 98 % recomendó seguir utilizándolo. Conclusiones: El uso del simulador facilita la adquisición de competencias y estimula el aprendizaje en el estudiante, lo cual puede ser atribuido a la práctica deliberada, a un mayor tiempo de exposición y a la interacción cognitiva.

Abstract Introduction: Heart exploration is an essential clinical competence that requires continuous training and exposure. Low availability and accessibility to patients with heart disease constitutes a barrier to acquiring this competence. Inadequate cardiac auscultation skills in medical students, residents, and graduate physicians have been documented. Objective: To develop and validate a low-cost, high-fidelity simulator for heart exploration. Methods: A low-cost, high-fidelity heart examination simulator capable of reproducing normal cardiac sounds was designed and developed. Subsequently, the simulator was validated by a group of experts who gave their opinion according to a Likert scale. Results: Ninety-four percent agreed that the simulator motivates the learning of heart exploration, and 92 % considered it to be a realistic model; 91 % considered that the simulator is an attractive tool to reinforce learning and 98 % recommended its further use. Conclusions: The use of the simulator facilitates the acquisition of skills and stimulates learning in the student, which can be attributed to repeated practice, longer exposure time and cognitive interaction.

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End-stage kidney disease (ESKD) is a worldwide unsolved problem. Access to renal replacement therapies (RRT) is still a challenge in some developed countries and even more so in developing countries. Allo-hemodialysis (alloHD) is a recently proposed, still hypothetical, alternative RRT where the blood of a healthy subject ("buddy") flows countercurrent to the patient's blood through the dialyzer. Solutes and fluid are transferred to the buddy and then cleared by his/her healthy kidneys, making alloHD essentially a procedure where the buddy "donates" kidney function intermittently to the patient. Its drastically reduced complexity makes -alloHD particularly attractive for low-resource settings. The acceptance of alloHD by patients, caregivers, and health care professionals (HCP) is unknown. In this cross-sectional study, we surveyed the preferences and acceptance of alloHD in 3 groups: caregivers related to ESKD patients, nonrelated caregivers (nrCG), and HCP. Four areas were explored: RRT preferences, kidney organ donation for transplant acceptance, -alloHD acceptance as a potential RRT, and alloHD technique acceptance. Hemodialysis was the preferred form of RRT. Kidney donation acceptance was similar in all groups. Intermittent kidney function donation (i.e., alloHD) was mainly accepted by related and nrCG but less accepted by HCP (87, 90, and 60% respectively, p < 0.01). New RRT alternatives such as alloHD are expected to be better received and accepted once animal, and clinical studies have demonstrated their feasibility, safety, and benefits. New RRT strategies are required primarily in most vulnerable populations and should be explored.

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BACKGROUND AND OBJECTIVES: Current hemodialysis techniques fail to efficiently remove the protein-bound uremic toxins p-cresyl sulfate and indoxyl sulfate due to their high degree of albumin binding. Ibuprofen, which shares the same primary albumin binding site with p-cresyl sulfate and indoxyl sulfate, can be infused during hemodialysis to displace these toxins, thereby augmenting their removal. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We infused 800 mg ibuprofen into the arterial bloodline between minutes 21 and 40 of a conventional 4-hour high-flux hemodialysis treatment. We measured arterial, venous, and dialysate outlet concentrations of indoxyl sulfate, p-cresyl sulfate, tryptophan, ibuprofen, urea, and creatinine before, during, and after the ibuprofen infusion. We report clearances of p-cresyl sulfate and indoxyl sulfate before and during ibuprofen infusion and dialysate concentrations of protein-bound uremic toxins normalized to each patient's average preinfusion concentrations. RESULTS: We studied 18 patients on maintenance hemodialysis: age 36±11 years old, ten women, and mean vintage of 37±37 months. Compared with during the preinfusion period, the median (interquartile range) clearances of indoxyl sulfate and p-cresyl sulfate increased during ibuprofen infusion from 6.0 (6.5) to 20.2 (27.1) ml/min and from 4.4 (6.7) to 14.9 (27.1) ml/min (each P<0.001), respectively. Relative median (interquartile range) protein-bound uremic toxin dialysate outlet levels increased from preinfusion 1.0 (reference) to 2.4 (1.2) for indoxyl sulfate and to 2.4 (1.0) for p-cresyl sulfate (each P<0.001). Although median serum post- and predialyzer levels in the preinfusion period were similar, infusion led to a marked drop in serum postdialyzer levels for both indoxyl sulfate and p-cresyl sulfate (-1.0 and -0.3 mg/dl, respectively; each P<0.001). The removal of the nonprotein-bound solutes creatinine and urea was not increased by the ibuprofen infusion. CONCLUSIONS: Infusion of ibuprofen into the arterial bloodline during hemodialysis significantly increases the dialytic removal of indoxyl sulfate and p-cresyl sulfate and thereby, leads to greater reduction in their serum levels.

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BACKGROUND: Central venous oxygen saturation (ScvO2) is correlated with cardiac output. In most patients, ScvO2 declines during hemodialysis (HD) due to factors such as reduced preload, myocardial stunning, and intermittent arrhythmias. Previous research has shown that low ScvO2 is associated with higher mortality in chronic HD patients. In this research, we tested the hypothesis that ScvO2 variability is associated with all-cause mortality. METHODS: We conducted a retrospective study in 232 chronic HD patients with central venous catheter as vascular access. ScvO2 was recorded 1× per minute during dialysis using the Crit-Line monitor. A 6-month baseline comprising at least 10 dialysis treatments with ScvO2 recordings preceded a follow-up period of up to 3 years. The coefficient of variation (CV) of ScvO2 (100 times the ratio of the standard deviation and mean of ScvO2) served as a measure of ScvO2 stability during baseline. Patients were stratified by median population CV of ScvO2 during baseline, and survival during follow-up was compared between the 2 groups by Kaplan Meier and multivariate Cox analysis. The association between CV of ScvO2 and all-cause mortality during follow-up was further assessed by Cox analysis with a spline term for CV of ScvO2. RESULTS: The mean CV ± standard deviation of ScvO2 in our population was 6.1 ± 2.7% and the median was 5.3%. Univariate Kaplan-Meier analysis (p = 0.043) and multivariate Cox analysis (hazard ratio [HR] 1.16; p = 0.0005) indicated that a CV of ScvO2 > 5.3% was significantly associated with increased mortality. In Cox analysis with spline term, a CV of ScvO2 >  11% was associated with a significantly increased HR for all-cause mortality. CONCLUSION: High ScvO2 variability during dialysis is associated with increased all-cause mortality.

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BACKGROUND: The time between the creation of an arteriovenous fistula (AVF) and its successful use is significantly longer in hemodialysis (HD) patients in the United States compared to those in other countries, and there is an urgent need to reduce the residence time of central-venous catheters (CVC). METHODS: Successful AVF creation and maturation results in typical hemodynamic changes, such as an increase in cardiac output and upper body blood flow (UBBF). In patients with CVC as vascular access, we measured once per minute intradialytic central-venous oxygen saturation (ScvO2) and hemoglobin levels simultaneously using the Crit-Line Monitor. Under conditions of stable upper body oxygen consumption and arterial oxygen saturation, ScvO2 and hemoglobin concentration allows the calculation of estimated UBBF (eUBBF). In a quality improvement project, we used ScvO2 and eUBBF to track the hemodynamic changes accompanying AVF maturation. RESULTS: Out of 11 patients (9 incident to HD, 1 female, age 61 ± 13 years), AVF maturation was successful in 9. In 1 patient, the AVF did not mature. One patient died from sudden cardiac death with a maturing AVF. In the 9 patients with successful AVF maturation, ScvO2 increased from 60.9 ± 2.7% prior to AVF creation to 73.4 ± 3.6% a week after AVF creation (19.6 ± 6.3% increase). eUBBF increased from 1.3 ± 0.3 to 2.2 ± 0.6 L/min (62.7 ± 37.5% increase); no material ScvO2 or eUBBF changes occurred in the other 2 patients. CONCLUSION: Our results indicate the potential utility of ScvO2 and eUBBF to track the hemodynamic response to AVF maturation. To what extent these insights translate into shortening of the time between AVF creation and successful cannulation warrants further investigations.

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BACKGROUND/AIMS: Neighborhood walkability is associated with indicators of health in the general population. We explored the association between neighborhood walkability and daily steps in hemodialysis (HD) patients. METHODS: We measured daily steps over 5 weeks using Fitbit Flex (Fitbit, San Francisco, CA, USA) and retrieved Walk Score® (WS) data by patient's home ZIP code (www.walkscore.com; 0 = poorest walkability; 100 = greatest walkability). RESULTS: HD patients took a mean of 6,393 ± 3,550 steps/day (n = 46). Median WS of the neighborhood where they resided was 28. Patients in an above-median WS (n = 27) neighborhood took significantly more daily steps compared to those (n = 19) in a below-median WS neighborhood (7,514 ± 3,900 vs. 4,800 ± 2,228 steps/day; p < 0.001, t test). Daily steps and WS were directly correlated (R = 0.425; p = 0.0032, parametric test; R = 0.359, p = 0.0143, non-parametric test). CONCLUSION: This is the first study conducted among HD patients to indicate a direct relationship between neighborhood walkability and the actual steps taken. These results should be considered when designing initiatives to increase and improvise exercise routines in HD populations.

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Background: Cardiac disease is highly prevalent in hemodialysis (HD) patients. Decreased tissue perfusion, including cardiac, due to high ultrafiltration volumes (UFVs) is considered to be one of the drivers of cardiac dysfunction. While central venous oxygen saturation (ScvO2) is frequently used as an indicator of cardiac output in non-uremic populations, the relationship of ScvO2 and UFV in HD patients remains unclear. Our aim was to determine how intradialytic ScvO2 changes associate with UFV. Methods: We conducted a 6-month retrospective cohort study in maintenance HD patients with central venous catheters as vascular access. Intradialytic ScvO2 was measured with the Critline monitor. We computed treatment-level slopes of intradialytic ScvO2 over time (ScvO2 trend) and applied linear mixed effects models to assess the association between patient-level ScvO2 trends and UFV corrected for body weight (cUFV). Results: We studied 6042 dialysis sessions in 232 patients. In about 62.4% of treatments, ScvO2 decreased. We observed in nearly 80% of patients an inverse relationship between cUFV and ScvO2 trend, indicating that higher cUFV is associated with steeper decline in ScvO2 during dialysis. Conclusions: In most patients, higher cUFV volumes are associated with steeper intradialytic ScvO2 drops. We hypothesize that in a majority of patients the intradialytic cardiac function is fluid dependent, so that in the face of high ultrafiltration rates or volume, cardiac pre-load and consequently cardiac output decreases. Direct measurements of cardiac hemodynamics are warranted to further test this hypothesis.

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Central venous oxygen saturation (ScvO2) in the superior vena cava is predominantly determined by cardiac output, arterial oxygen content, and oxygen consumption by the upper body. While abnormal ScvO2 levels are associated with morbidity and mortality in non-uremic populations, ScvO2 has received little attention in hemodialysis patients. From 1/2012 to 8/2015, 232 chronic hemodialysis patients with central venous catheters as vascular access had their ScvO2 monitored during a 6-month baseline period and followed for up to 36 months. Patients were stratified into upper and lower two tertiles by a ScvO2 of 61.1%. Survival analysis employed Kaplan-Meier curves and adjusted Cox proportional hazards models. Patients in the lower tertiles of ScvO2 were older, had longer hemodialysis vintage, lower systolic blood pressure, lower ultrafiltration rates, higher leukocyte counts and neutrophil-to-lymphocyte ratios. Kaplan-Meier analysis indicated a shorter survival time in the lower tertiles of ScvO2 (P = 0.005, log-rank test). In adjusted Cox analysis, a 1 percent point decrease in mean ScvO2 was associated with a 4% increase in mortality (HR 1.04 [95% CI 1.01-1.08], P = 0.044), indicating that low ScvO2 is associated with poor outcomes. Research on the relative contributions of cardiac output and other factors is warranted to further elucidate the pathophysiology underlying this novel finding.

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BACKGROUND/AIMS: In hemodialysis (HD) patients the endothelial and erythrocyte glycocalyx is impaired which in turn correlates with elevated erythrocyte sodium sensitivity (ESS). Additionally, apoptotic erythrocyte death (eryptosis), characterized by phosphatidylserine (PS) exposure on the cell surface, is increased in this population. We aimed to explore the relationship of ESS and eryptosis. METHODS: Blood samples were collected from 11 healthy controls and 20 chronic HD patients before and after midweek HD. ESS was quantified by the salt blood test. PS-exposure, intracellular reactive oxygen species (ROS) of erythrocytes and reticulocytes were assessed by flow cytometry. RESULTS: Compared to controls ESS was significantly higher in HD patients preHD and did not change during treatment. The percentage of eryptotic cells did not differ between controls and patients preHD. However, eryptosis decreased during HD. ESS and eryptosis were uncorrelated, while eryptosis was positively correlated with intracellular ROS and percent reticulocytes. CONCLUSIONS: Higher ESS levels in HD patients indicate a pathologic glycocalyx. ESS and eryptosis were not correlated. The decreased eryptosis postHD may possibly be related to dialytic uremic toxin removal, but is likely multifactorial. The relationship between eryptosis and intracellular ROS warrants further research.

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When kidney failure occurs, patients are at risk for fluid overload states, which can cause pulmonary edema, pleural effusions, and upper airway obstruction. Kidney disease is also associated with impaired respiratory function, as in central sleep apnea or chronic obstructive pulmonary disease. Hence, respiratory and renal diseases are frequently coexisting. Hypoxemia is the terminal pathway of a multitude of respiratory pathologies. The measurement of oxygen saturation (SO2) is a basic and commonly used tool in clinical practice. Both arterial oxygen saturation (SaO2) and central venous oxygen saturation (ScvO2) can be easily obtained in hemodialysis (HD) patients, SaO2 from an arteriovenous access and ScvO2 from a central catheter. Here, we give a brief overview of the anatomy and physiology of the respiratory system, and the different technologies that are currently available to measure oxygen status in dialysis patients. We then focus on literature regarding intradialytic SaO2 and ScvO2. Lastly, we present clinical vignettes of intradialytic drops in SaO2 and ScvO2 in association with different symptoms and clinical scenarios with an emphasis on the pathophysiology of these cases. Given the fact that in the general population hypoxemia is associated with adverse outcomes, including increased mortality, cardiac arrhythmias and cardiovascular events, we posit that intradialytic SO2 may serve as a potential marker to identify HD patients at increased risk for morbidity and mortality.

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Assessment of arterio-venous fistula (AVF) blood flow (ABF) is vital in hemodialysis (HD) patients. Currently, no non-invasive and contact-free technique is available to accurately measure ABF in routine clinical practice. In this study, we developed a novel approach using video image processing (VIP) to measure the change in optic flow in the skin. We the tested the hypothesis that the change in optical flow, expressed as the change in pixels between consecutive frames, is related to ABF. We recorded AVF videos in 40 HD patients using a digital camera and processed them by VIP technique. We then compared the actual ABF as measured by routine online clearance (ABFOLC) and the amplitude (AMP) of optical flow. Technical and procedural errors rendered VIP invalid in 13 patients. In the remaining 27 patients the optical flow AMP was significantly lower in patients with low (<;900 ml/min) ABFOLC compared to patients with normal (≥900 ml/min) ABFOLC (AMP 3.4±1*103 vs 5.2±1.4 *103 [pixels], p<;0.01). In these 27 patients AMP correlated with ABFOLC (R2=0.71, p<;0.0001). While more extensive research is necessary, these preliminary results indicate the potential usefulness of the VIP technique to identify low ABF.

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O cancer é uma das principais causas de morte no mundo, e a busca da cura desse mal é uma das principais preocupações da medicina moderna. Neste sentido, na última década dois nomes têm se destacado no estudo do crescimento tumoral e a busca da cura: Judah Folkman e Michael O`Reilly. Seus estudos sobre a angiogênese tumoral permitiram a identificação de dois agentes, angiostatina e endostatina, que mostram grande potencial na terapêutica antineoplásica, agindo justamente na inibição dessa angiogênese. O marco desse estudo foi a observação clínica e laboratorial do rápido crescimento e disseminação de imúmeros focos tumorais após a retirada de um tumor primário. Conclui-se, portanto, que a presença deste inibia de alguma forma o crescimento dos demais focos. Essas duas novas substâncias vêm se somar às várias terapias antiangiogênicas tumorais em estudo, como o trombospondin, interferon, inibidores das metaloproteinases; porém com a vantagem de serem até o presente momento, sem efeitos colaterais...

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